Drug abuse is a critical problem throughout the world. Commonly abused drugs include cocaine, cannabinoids, amphetamine, phencyclidine (PCP), as well as designer drugs such as 3,4-methelenedioxyamphetamine (meth) 3,4-methelenedioxy-methamphetamine (Ecstasy) and others.
On Sep. 15, 1986, President Reagan issued Executive Order No. 12564 directing federal agencies to achieve a drug-free work environment. The Department of Health and Human Services (HHS) has developed guidelines and protocols for drugs-of-abuse testing. The mandatory Guidelines for Federal Workplace Drug Testing Programs were first published in the Federal Register on Apr. 11, 1988, and that were since revised on Jun. 9, 1994, and on Sep. 30, 1997. Another notice was issued on Apr. 13, 2004.
It is estimated that approximately 20 million employees are screened each year for illicit drug use. Drug testing programs in the United States can be classified as mandatory or non-mandatory. In the mandatory programs (e.g., the Department of Transportation), a regulated employer is required by federal regulation to test employees. In the non-mandatory programs, employers choose to test for reasons other than federal regulations.
Persons using drugs may attempt to adulterate urine specimens to avoid detection. Adulterants are substances that can be added to a urine sample to affect the integrity of the sample and results of the laboratory assays used to detect drugs of abuse (DOA). These adulterants are often oxidants that destroy, or partially destroy, evidence of DOA in a urine sample. Thus, both screening and confirmatory tests can be rendered negative. Oxidant adulterants include potassium nitrite (e.g., “Klear” and “Whizzies”), potassium chlorochromate (e.g., “Urine Luck”) and hydrogen peroxide/peroxidase (e.g., “Stealth”) and are readily available, usually at low cost. Household bleach is also an effective adulterant that can cause negative DOA results. Adulterants can degrade and disappear in a sample within hours after being added, making them difficult or impossible to detect. Further, specific tests have to be conducted to detect each type of adulterant.
DOA testing often involves several steps, which can include: (a) sample collection, (b) sample integrity testing, (c) DOA Screening, and (d) confirmatory tests. These steps may: (a) occur at different locations, (b) be conducted by personnel with varying qualifications, (c) be conducted by different institutions, and/or (d) be conducted sequentially at different times. For example, confirmatory tests are conducted after the screening tests and often required that the sample be transported from one institution or laboratory to another. The steps leading to the confirmatory testing step may occur over one or more days.
Laboratories typically screen samples using commercially available enzyme immunoassays (EIA) and related methods and reagents. These screening methods are not always completely specific as there can be cross-reacting substances that can cause false positive results. Consequently, cut-off values or minimum concentrations for each drug have been established, whereby assayed values below the cut-off value are considered negative results. If a positive result is obtained by the EIA screen, the sample can be sent to a confirmatory testing laboratory where Gas Chromatory/Mass Spectrophometry equipment is often utilized for the confirmatory test. Generally, the cut-off values used for the confirmatory test are lower than the values used for the initial screening (EIA). In general, only initially positive screening tests are submitted for confirmatory testing and the confirmatory test results are considered conclusive. Because of the cut-off value criteria used to establish a positive result in these tests, adulterants only need to lower the tested value of the urine sample below the cut-off level to produce an accepted negative result.
Federal guidelines by the U.S. NRC, 10 CFR 26.161 require that specimen integrity tests be performed by HHS-certified laboratories. Clinical laboratory professional organizations have called attention to the problems with adulterated urine samples for illicit drug testing; however, detecting an adulterated urine sample is difficult. The American Journal of Clinical Pathology concluded that new adulterants can produce false negative results for DOA. The Substance Abuse and Mental Health Services Administration (SAMHSA) reports that of 6,320,000 samples tested in 2013 one of every 300 was invalid. If the adulterant testing procedures failed to detect “disappearing” adulterants, that number may have been even higher. The invalid tests may also be much higher in non-mandated labs or other labs not performing adequate tests for adulterants.
Manual spot tests have become available to test for the presence of adulterants in a sample. Although a step in the right direction in detecting adulterants, these tests can be laborious and expensive to perform and primarily provide only qualitative results, which may still result in under-detection or false positives. The high cost of these manual tests may lead non-mandated laboratories to take short cuts in adulterant testing, partially because reimbursement for adulterant testing has been uncommon. Recently the reimbursement for DOA testing has been reduced with the reimbursement for confirmatory testing reduced more than that for EIA screening tests. Previously, some adulterant testing was reimbursed; but, under the new reimbursement for DOA the adulterant screening is included in the reimbursement for DOA testing. It appears that now, labs not doing adulterant screening are not doing all of the testing for which they are paid. Adulterant testing products and labor can be costly, and the cost is escalating, causing non-mandated laboratories to forego adulterant testing. Ironically, clinical laboratory testing costs in general are one of the few areas in health care where costs of an individual diagnostic test have declined since the 1950′s. That reduction in cost has been brought about by laboratory automation and the integration of the automation with laboratory/hospital information systems. The use of automated systems, methods, and reagents combined with automated sample identification and documentation by an integrated Laboratory Information System computer would enable the costs to be reduced to a fraction of the costs of manual adulteration spot test, if a reagent were available.
A wide variety of oxidative-adulterants is available that can avoid detection of DOA, and new ones are regularly introduced into the market. Testing all samples for specific oxidants would be very expensive. As such, ideally a general oxidant-screening test could be used to determine and provide evidence that an oxidative-adulterant may have been used to adulterate a sample, as opposed to testing samples for the presence of specific adulterants.
Prior art automated screening for oxidant adulteration employs General Oxidant detecting reagents, which are intended to detect the presence of an oxidative-adulterant; however, nitrite, a commonly used oxidant adulterant, may be naturally present in low concentration in urine due to, for example, a bacterial presence in the urinary tract or use of certain therapeutic drugs. Consequently, in an effort to minimize or inhibit these samples from being tested positive for DOA, the tests use an oxidizing equivalence of 200-500 units of nitrite as a lower cutoff level.
In addition, adulterant testing can be performed by the confirmatory laboratory hours or days after an adulterant would have been added to the sample. Because of the multiple steps in the DOA testing process, the result can be positive at the time of testing by the screening lab, but negative when tested some time later by the confirmatory lab. This can allow an adulterant, such as Stealth, to degrade or “disappear” to a level below those above-mentioned by the time testing is conducted. Thus, such a sample can pass adulteration screening tests for a General Oxidant. Further, the adulterant may continue to destroy the drug of abuse during the delay period before disappearing, thereby avoiding detection of both in the screening tests.
As previously indicated, new adulterants are being introduced periodically. Stealth-type products (which include hydrogen peroxide + peroxidase) are known to effectively escape detection. It is therefore likely that other types of oxidants having the “disappearing” nature of Stealth will be favored by those profiting from the sale and use of adulterants.